Mechanisms of Active DNA Demethylation in somatic cells (770)

Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

Department of Pathology, Christchurch School of Medicine, University of Otago , Christchurch, New Zealand

While, every cell in an organism is genetically identical there are marked phenotypic differences between tissues and organs that are controlled by epigenetic modifications. The most stable epigenetic modification is methylation of cytosine. Many cancers show significant global loss of methylation. Our research investigates the mechanism of changes in DNA methylation as they occur during human life using a barcoded hairpin-bisulphite sequencing technique. We have observed rapid demethylation in cultured Jurkat cells (T cell leukaemia) implicating novel mechanisms of active demethylation that have not yet been recognised by researchers in the field. It is likely that the demethylation pathways that we are studying operate during the onset of cancer and the existence of molecules (ascorbate or transition metals) that alter ten-eleven translocation (TET) activity may have implications for modification of this process. While there is a substantial amount to be done before making therapeutic or dietary recommendations, our results might provide a rationale for long-term intervention to alter an individual’s epigenetic risk.